Natsuka S, Takubo R, Seki R, Ikura K
Department of Applied Biology, Faculty of Textile Science, Kyoto Institute of Technology, Kyoto 606-8585, Japan.
J Biochem. 2001 Dec;130(6):731-5. doi: 10.1093/oxfordjournals.jbchem.a003042.
Formation of cross-linking between proteins via a gamma-glutamyl-epsilon-lysine residue is an important process in many biological phenomena including apoptosis. Formation of this linkage is catalyzed by the enzyme transglutaminase, which is widely distributed from bacteria to the animal kingdom. The simple multi-cellular organism Caenorhabditis elegans also possesses transglutaminase activity associated with apoptosis [Madi, A. et al. (1998) Eur. J. Biochem. 253, 583-590], but no gene with significant homology to vertebrate or bacterial transglutaminases has been found in the C. elegans genome sequence database. On the other hand, protein disulfide isomerases were recently recognized as a new family of transglutaminases [Chandrashekar, R. et al. (1998) Proc. Natl. Acad. Sci. USA 95, 531-536]. To identify the molecule with transglutaminase activity in C. elegans, we isolated from C. elegans a gene homologous to ERp57, which encodes a protein disulfide isomerase, expressed it in recombinant form, and characterized the transglutaminase and protein disulfide isomerase activities of the resultant protein. The C. elegans ERp57 protein had both enzyme activities, and the transglutaminase activity had similar characteristics to the activity in lysate of the whole worm. These results suggested that the ERp57 homologue was one of the substances with transglutaminase activity in C. elegans.
蛋白质通过γ-谷氨酰-ε-赖氨酸残基形成交联是包括细胞凋亡在内的许多生物学现象中的一个重要过程。这种交联的形成由转谷氨酰胺酶催化，该酶广泛分布于从细菌到动物界的各个物种。简单的多细胞生物秀丽隐杆线虫也具有与细胞凋亡相关的转谷氨酰胺酶活性[马迪，A.等人（1998年）《欧洲生物化学杂志》253卷，583 - 590页]，但在秀丽隐杆线虫基因组序列数据库中未发现与脊椎动物或细菌转谷氨酰胺酶具有显著同源性的基因。另一方面，蛋白质二硫键异构酶最近被确认为转谷氨酰胺酶的一个新家族[钱德拉谢卡尔，R.等人（1998年）《美国国家科学院院刊》95卷，531 - 536页]。为了鉴定秀丽隐杆线虫中具有转谷氨酰胺酶活性的分子，我们从秀丽隐杆线虫中分离出一个与ERp57同源的基因，该基因编码一种蛋白质二硫键异构酶，以重组形式表达它，并对所得蛋白质的转谷氨酰胺酶和蛋白质二硫键异构酶活性进行了表征。秀丽隐杆线虫的ERp57蛋白具有这两种酶活性，且其转谷氨酰胺酶活性具有与整个线虫裂解物中的活性相似的特征。这些结果表明，ERp57同源物是秀丽隐杆线虫中具有转谷氨酰胺酶活性的物质之一。
